DESCRIPTION: The long-term goal of this research project is to facilitate the appropriate diagnosis and, ultimately, the successful treatment of patients with periodontal disease. Although specific bacteria of the Dental plaque biofilm are considered to be causative of periodontitis, it is the host's variable immuno-inflammatory response to the bacterial challenge that is largely recognized as the key determinant of the type, the extent and the severity of the disease. This response is thought to have a strong genetic component. Currently, the differential diagnosis of the major forms of periodontitis (chronic and aggressive) is primarily based on clinical signs after consideration of medical and oral health history. Nevertheless, the clinical presentation of both types of disease may be quite similar, and the response of both to standard therapeutic procedures may vary considerably. Importantly, a biologic basis for the distinction between chronic and aggressive periodontitis has not been well documented. [unreadable] [unreadable] The proposed project is based on the hypothesis that distinct forms of periodontitis can be identified based on local gene expression in pathological periodontal tissues. We plan to take advantage of contemporary gene expression profiling technology to investigate whether chronic and aggressive periodontitis are sufficiently distinct with respect to their pathobiology. A total of 120 patients, 60 with chronic and 60 with aggressive periodontitis will be recruited. Samples of inflamed gingival tissue will be obtained from each patient and will be analyzed with respect to local patterns of gene expression using microarrays. In addition, periodontal microbiota and systemic antibody responses will be characterized with respect to 20 bacterial species by means of checkerboard DNA-DNA hybridizations and checkerboard immunoblotting, respectively. The first Aim of this application is to examine the differential gene expression in inflamed periodontal tissues of patients with chronic and aggressive periodontitis. This analysis will elucidate whether the currently accepted diagnostic classification has a solid molecular basis. The second Aim is to explore a novel classification scheme based on similarities in gene expression signatures, and validate it against relevant clinical, microbiological and serological markers of periodontitis. Ultimately, a pathobiology-based classification of periodontitis will facilitate correct diagnosis and targeted, efficient therapeutic prevention and intervention strategies. [unreadable] [unreadable]